Re-iterative Strategies for the Synthesis of Polycyclic Ethers

Polycyclic ethers are a class of large natural products isolated from marine algae. Their highly complex structure combined with low natural abundance leads to challenges in studying their potential medicinal uses. As such, synthesis is the best possible option to obtain these polycyclic ethers. On the instigation of A/Prof Christopher S. P. McErlean, in Chapter 2, I investigated the use of an α-keto acid for the re-iterative synthesis of polycyclic ethers. The synthesis of an initial ring to build complexity was followed by attempts at synthesising the α-keto acid which proves to be unstable. The use of the trimethylsilyl (TMS) protecting group allows for a novel TMS-shuttle conjugate addition to achieve the desired product. Additionally, further exploration of the novel TMS-shuttle conjugate addition is pursued. In Chapter 3, shifting focus to acyl radical formation. Using tetra-n-butylammonium decatungstate (TBADT) for acyl generation, enables us to develop a protocol to allow for easy access to a large quantity of desired cyclised product with different attached moieties. In addition, we explore another re-iteravtive strategy was possible using TBADT to achieve chemoselective addition. In Chapter 4, we explore chemical education in partnership with the Department of Pharmacology to create a new laboratory practical for undergraduate students. We develop and optimise the synthesis of matrix metalloproteinases inhibitors so that students are able to undertake the practical in a safe and time efficient manner